Nitrogen → HCID 53629073, Verbindung

HRID 1163217Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1163217
I[C:2]1[N:3]=[C:4]([CH:12]2[CH2:15][CH:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.[F:23][C:24]1[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:27]=[C:28]2[C:33]=1[N:32]=[C:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH:30]=[CH:29]2.C(=O)([O-])[O-].[Cs+].[Cs+].N#N.C([O-])(O)=O.[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:23][C:24]1[C:25]([C:2]2[N:3]=[C:4]([CH:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)[CH2:13]3)[N:5]3[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=23)=[CH:26][CH:27]=[C:28]2[C:33]=1[N:32]=[C:31]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH:30]=[CH:29]2

Komponenten

9

Edukt 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 536290468-Fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinolineHCID 576810251-Iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine

Produkt 1

HCID 53629073HCID 53629073, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A solution of 1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine (93 mg, 0.22 mmol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline (87 mg, 0.25 mmol) and cesium carbonate (88 mg, 0.27 mmol) in DME (3.33 mL) and H2O (0.67 mL) was degassed with N2 for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.011 mmol) was added, and the reaction heated at 75° C. overnight. The reaction was allowed to cool to rt, poured into saturated NaHCO3 solution (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organics were washed with brine (3×50 ml), dried (MgSO4), filtered and concentrated in vacuo. Flash chromatography (DCM stepping up to 5% MeOH in DCM) gave the title compound as an off-white solid; 1H NMR (CDCl3, 400 MHz) δ 8.27 (1H, d, J-8.6 Hz), 8.23 (2H, d, J=7.1 Hz), 7.99 (1H, d, J=8.8 Hz), 7.73-7.67 (2H, m), 7.55-7.48 (3H, m), 7.16 (1H, d, 5.1 Hz), 7.06 (1H, d, J=5.1 Hz), 3.46 (1H, m), 2.94 (1H, m), 2.71-2.32 (15H, m); MS (ES+): m/z 508.03 [MH+]; HPLC: tR=1.71 min (MicromassZQ, polar—5 min).

Aufarbeitung

  1. temperatureto cool to rt
  2. extractionextracted with ethyl acetate (3×50 ml)
  3. washThe combined organics were washed with brine (3×50 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-b5a54d5fb174409badcc74dcdfbaecdd
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07820662B2

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